合成路线1

N-Boc glutamic acid delta-benzyl ester (VI) was treated with carbonyldiimidazole (CDI) in THF, and to the resulting acyl imidazole was added MeOH to provide alpha-methyl ester (VII). Further hydrogenolysis of (VII) in the presence of palladium on carbon cleaved the benzyl ester to give acid (VIII). Treatment of (VIII) with ethanethiol in the presence of EDC and DMAP yielded thioester (IX) and this was then reduced with triethylsilane in the presence of Pd-C to glutamic semialdehyde (X), which was shown to exist predominately in the hemiaminal form (XI). Condensation of this aldehyde (XI) with cysteine (XII) led, via the intermediate thiazolidine (XIII), to the bicyclic lactam (XIV) after equilibration to the more stable isomer. Formation of methyl ester (XV) via the acyl imidazole intermediate, followed by trifluoroacetic acid-catalyzed deprotection of the Boc group of (XV) afforded the amine salt (XVI). This was treated with benzylsulfonyl chloride (XVII) in the presence of collidine to give sulfonamide (XVIII), and subsequent ester hydrolysis provided acid (XIX). Coupling of this acid with amino acetal (V) by treatment with EDC and HOBt yielded amide (XX). Finally, hydrolysis of the acetal of (XX) with dilute HCl in acetonitrile, with simultaneous deblocking of both guanidino-Boc groups and cyclization afforded the title compound, which was purified by reverse phase HPLC, and converted to the trifluoroacetate salt.